Genotype-specific susceptibilities to the induction of neuroblastoma and fiborasarcoma/rhabdomyosarcoma by the direct-acting carcinogen N-methyl-N-nitrosourea (MNU) have recently been demonstrated in interspecific backcross hybrids of fishes of the genus Xiphophorus. By following the segregation of a single genetic pigmentation marker from one of the parental species in MNU-exposed backcross hybrids at least two different chromosomes were shown to be related to tumor inducibility. Genetic susceptibility and modifier factors have been postulated. In this research project, we will take advantage of over 40 enzyme locus polymorphisms among the parental strains used to produce backcross hybrids. Alleles at these polymorphic loci, identifiable by starch gel electrophoresis and histochemical staining, exhibit Mendelian segregations in interspecific backcross hybrids and therefore can be used to detect associations between tumor inducibility factors and biochemical loci through genetic linkage analyses. Biochemical markers shown to be closely linked to tumor inducibility factors will then be brought together into a single strain by pregenotyping and selective breeding to produce maximally susceptible fish. We therefore envision the production of an aquatic vertebrate in vivo system for use in the evaluation of putative carcinogens and in the analysis of the biochemical genetics of the carcinogenic process.